Merck Sharp & Dohme LLC - IPR2026-00312

Notice filing date accorded

U.S. Patent No. 10,865,400

File History of U.S. Patent No. 10,865,400 Part 1

File History of U.S. Patent No. 10,865,400 Part 2

File History of U.S. Patent No. 10,865,400 Part 3

United States Patent Publication No. 2013/0302275

U.S. Patent No. 7,767,429

Chao, Structure of Human Hyaluronidase-1 (2007)

WO 2010/077297, published 8 July 2010

Stern, The Hyaluronidases: Their Genomics, Structures, & Mechanisms (2006)

Jedzrejas, Structures of Vertebrate Hyaluronidases (2005)

Zhang, Hyaluronidase Activity of Human Hyal1 (2009)

Arming, In vitro Mutagenesis of PH-20 Hyaluronidase from Human Sperm (1997)

Bordoli, Protein Structure Homology Modeling Using SWISSMODEL (2008)

Frost, Recombinant Human Hyaluronidase (rHuPH20) (2007)

Branden & Tooze, Introduction to Protein Structure (1999) Part 1

Branden & Tooze, Introduction to Protein Structure (1999) Part 2

Table Associating ’400 Patent to Corresponding ’731 Application and US-275

Steipe, Consensus-Based Engineering of Protein Stability (2004)

Green, Computer Graphics, Homology Modeling, and Bioinformatics (2010)

Chica, Semi-rational Approaches to Engineering Enzyme Activity (2005)

Hardy, Assessment of Contraceptive Vaccines Based on Recombinant (2004)

Pomering, Restricted Entry of IgG (2002)

Baba, Mouse Sperm Lacking Cell Surface Hyaluronidase PH-20 (2002)

Primakoff, Reversible Contraceptive Effect of PH-20 Immunization (1997)

Tung, Mechanism of Infertility in Male Guinea Pigs Immunized with Sperm

Rosengren, Recombinant Human PH20 (2018)

U.S. Patent Application No. 13/694,731

2024 Chemistry Nobel Prize Background

Bordier, Phase separation of integral membrane proteins (1981)

Gmachl, The Human Sperm Protein PH-20 Has Hyaluronidase Activity (1993)

Sills, “Retraction,” Science, 319:569 (2008)

Yue, Loss of Protein Structure Stability as a Major Causative Factor (2005)

Wang & Moult, SNPs, Protein Structure, and Disease (2001)

Marković-Housley, Crystal Structure of Hyaluronidase (2000)

“Negative Results,” Nature: Editorials, 453:258 (2008)

Hayden, Chemistry: Designer Debacle (2008)

Alberts, Molecular Biology of the Cell, Chapter 3 (2007)

He, NMR Structures of Two Designed Proteins with High Sequence Identity

Alexander, A Minimal Sequence Code for Switching Protein Structure (2009)

Ruan, Design & Characterization of a Protein Fold Switching Network (2023)

Redline Comparison of the ’731 and ’400 Specifications

Beasley & Hecht, Protein Design: The Choice of de Novo Sequences (1997)

Xiong, Periodicity of Polar and Nonpolar Amino Acids (1995)

Hayden, Key Protein-Design Papers Challenged (2009)

U.S. Patent Application No. 61/631,313

U.S. Patent Application No. 61/796,208

Leisola & Turunen, Protein Engineering: Opportunities and Challenges (2007)

Rosengren, Clinical Immunogenicity of rHuPH20 (2015)

Collection of SWISS-MODEL Webpages from the Internet Archive

Declaration of Jeffrey P. Kushan

Hunnicutt, Sperm Surface Protein PH-20 Is Bifunctional (1996)

Bookbinder, A Recombinant Human Enzyme for Enhanced Interstitial Transport

Goldberg, Protein Degradation and Protection (2003)

Vembar & Brodsky, One Step at a Time: Endoplasmic Reticulum-... (2008)

U.S. Publication 2010/0143457

Primakoff et al., Fully effective contraception in male and female...(1998)

Im, S. et al., Cryo-EM Structure of Human Hyaluronidase PH20 (2025)

Melanie Ann Simpson, Ph.D. Deposition Transcript

Gregory Petsko, Ph.D. Deposition Transcript

Dr. Naismith Analysis Spreadsheet

Dobson, Principles of protein folding, misfolding and aggregation (2004)

Dobson, Protein folding and misfolding (2003)

Dobson, Experimental investigation of protein folding and misfolding (2004)

Chiti & Dobson, Protein Misfolding, Functional Amyloid,...(2006)

Dobson, Protein misfolding, evolution and Disease (1999)

Goldsmith & Tawfik, Directed enzyme evolution: beyond...(2012)

Ochoa-Leyva et al., Protein Design through Systematic Catalytic...(2009)

Pal et al., Comprehensive and Quantitative Mapping of Energy...(2006)

van Rossum et al., Reporter-based screening and selection of enzymes (2013)

Reed et al., Use of Coefficient of Variation in Assessing... (2002)

Ten Have et al., Cloning and characterization of the cDNA... (1998)

Chowpongpang et al., Cloning and characterization of the bovine... (2004)

Fowler et al., High-resolution mapping of protein sequence function (2010)

Ringe & Petsko, Q&A: What are pharmacological chaperones (2009)

Calloni et al., Investigating the Effects of Mutations on Protein... (2005)

Chiti et al., Studies of aggregation of mutant proteins in vitro... (2002)

Chiti et al., Rationalization of the effects of mutations on... (2003)

Wang et al., Immunogenicity of protein aggregates-Concerns... (2012)

Poelwijk, Frank J., et al., Empirical fitness landscapes reveal... (2007)

Martin-Deleon, P., Epididymal SPAM1 and its Impact on Sperm Function (2006)

US-275 Activity Data and ’400 Patent Claims Comparison Spreadsheet

U.S. Food and Drug Administration, Medical Review, App. No. 21-859 (2005)

Redline of the ’731 App. and US-275 Publication

Petsko & Ringe, Protein Structure and Function (2004) Part 1

Petsko & Ringe, Protein Structure and Function (2004) Part 2

Petsko & Ringe, Protein Structure and Function (2004) Part 3

Petsko & Ringe, Protein Structure and Function (2004) Part 4

Nelson & Cox, Lehninger Principles of Biochemistry (2005)

Halozyme Therapeutics, Inc., Hylenex Label, U.S. FDA: Access Data (2005)

Declaration of Dr. James Naismith

Petition for Inter Partes Review of U.S. Patent No. 10,865,400

Petitioner's Power of Attorney